Activated Whole Blood Clotting Time Research Articles

Comparison of Activated Clotting Time to Hepcon Protamine Titration for Anticoagulation Management during Cardiopulmonary Bypass Surgery in a Patient with Severe Hemophilia a on Emicizumab Prophylaxis

Background: Emicizumab is a bispecific monoclonal antibody that bridges factor IXa and X, substituting the cofactor function of FVIII, but artificially shortens aPTT and interferes with aPTT-based assays. The activated whole blood clotting time (ACT) is the preferred point-of-care test to monitor anticoagulation with high-dose heparin in cardiopulmonary bypass (CPB). While theoretically ACT may be susceptible to the effects of emicizumab as the intrinsic pathway is involved, in vitro human clinical data suggest that emicizumab does not interfere with the ACT. There has been little experience managing patients with hemophilia A on emicizumab during CPB, and in most cases it is not feasible to delay surgery to await clearance of emicizumab due its long half-life. Heparin concentration by Hepcon protamine titration is an alternative monitoring method. Case: We describe the perioperative management of a patient with severe hemophilia A on maintenance emicizumab prophylaxis who underwent CPB with high-dose heparin monitored with both ACT and Hepcon. This 54-year-old male has a complex medical profile including Child Pugh B cirrhosis (baseline INR 1.5, platelets 100), Hepatitis C (treated), HIV on antiretroviral therapy (undetectable viral load), and remote portal vein thrombosis in the context of FEIBA and tranexamic acid use for a gastrointestinal bleed. He was diagnosed with Group B Streptococcus infective endocarditis. Despite optimal medical management, he developed aortic root abscess and aortic regurgitation necessitating operative intervention. A multidisciplinary team of hematology, cardiology, and cardiac surgery/anesthesia/intensive care deemed the risk of bleeding significant but not prohibitive and created a perioperative plan with liberal FVIII replacement followed by chromogenic FVIII levels postop (Table 1) to guide dosing. A bioprosthetic valve was chosen to reduce the need for postoperative anticoagulation. Emicizumab prophylaxis was continued. Intra-operative heparin titration was performed by the Hepcon point-of-care assay, but concurrent ACT measurements were taken to investigate the effect of emicizumab. INR, fibrinogen, hemoglobin, and platelet levels were measured as per surgical protocol. Preop FVIII replacement with moroctocog alfa (Xyntha®) (60 U/kg) was administered to target a ~120% FVIII level. Tranexamic acid was administered intraoperatively as per surgical protocol. He underwent a successful aortic valve replacement, bovine patch reconstruction and aortic root repair on CPB pump for a total of 175 minutes with no excessive intraoperative bleeding. Table 1 summarises the perioperative course, point-of-care testing results, hemostatic therapy, and FVIII levels. Following administration of protamine at the end of CPB (ACT 135s, Hepcon 0 U/mL) there was persistent oozing from the sternum which lessened with surgical packing and additional Xyntha®, but ultimately the chest was closed in favour of medical management. Two hours post-op there was ~1600mL of blood loss via chest tubes despite a FVIII level of 89%, platelets 147, and INR 1.7. Fibrinogen concentrate, fresh frozen plasma, and platelets were given prior to a repeat OR for exploration. Bleeding was confirmed from the sternal bone and muscle, and hemostasis was achieved with cautery and sutures. The remainder of the post-op course was uneventful with no further bleeding on emicizumab prophylaxis and FVIII replacement for 14 days. Discussion: The ACT and Hepcon results followed a similar trajectory over the operative course (Fig 1). Baseline and post-protamine ACT results were above normal reference range for non-anticoagulated patients (90-120s), and the intraoperative values were consistently above the target of 480s for CPB even when the Hepcon results fell below target (4.1 U/mL). The ACT results weren't artificially lowered with emicizumab, in fact elevated ACT values could have led to heparin underdosing risking circuit thrombosis. ACT is influenced by multiple variables including platelet count and function, antiphospholipids, factor deficiencies, temperature, and hemodilution. Therefore, the results may reflect derangements in one or more of these variables. We need further preclinical and clinical studies to better characterize the effect of emicizumab on ACT and identify the safest intraoperative monitoring strategy for patients on emicizumab requiring CPB surgery. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

P1052ASUPPRESSION OF BLOOD COAGULATION ON THE SURFACE OF A DIALYSIS MEMBRANE USING A DIALYSATE CONTAINING 800 PPM OF NITRIC OXIDE

Abstract Background and Aims Activation of platelets and leukocytes when blood comes in contact with a dialysis membrane surface leads to increased oxidative stress and release of proinflammatory cytokines, which may result in complications in dialysis patients. Within the blood vessels, nitric oxide (NO) generated by nitric oxide synthase on the endothelial cells suppresses both aggregation/activation of platelets and migration/adhesion of leukocytes. We previously showed in a rat hemodialysis model that NO (800 ppm) gas added to the dialysate can suppress blood coagulation on the surface of a dialysis membrane. The aim of the present study was to determine, using a rat hemodialysis model, the appropriate concentration of NO that would most effectively prevent blood coagulation without causing any adverse effects. Method Male Sprague Dawley rats weighing 300 to 400 g were used for the experiments. After the rats were anesthetized (isoflurane, 1.5%-3.0%), extracorporeal circulation was established by removal of blood from the carotid artery and returning it to the tail vein. During the experiment, the blood flow rate was kept at 1.0 mL/min, and the dialysate flow rate at 3 mL/min. Heparin was administered by bolus injection (0.7 unit/g-mouse) at the start of the hemodialysis, and no further heparin was added during the 4-hour hemodialysis session. A cellulose triacetate membrane and polymethylpentene membrane were used for making the small dialyzer and gas exchanger, respectively (the prototype module was manufactured by NIPRO, Co., Japan). NO (200 ppm, 400 ppm, or 800 ppm) was added to the dialysate via the gas exchanger in the NO groups, and N2 gas was added to the dialysate in the control group. During the experiment, the arterial pressure, dialyzer inlet pressure, venous pressure, activated whole blood clotting time (ACT) and methemoglobin (met-Hb) concentration were measured. After circulation, the amount of coagulated blood was measured by the hemoglobin (Hb) content and lactate dehydrogenase (LDH) activity in the eluate from the residual blood clotting in the dialyzer. Results The 4-hour hemodialysis session achievement rate was highest in the NO-800 ppm group (control, 54%; NO-200 ppm, 66%; NO-400 ppm, 77%; NO-800 ppm, 85%). The blood met-Hb content was below 10% in all the NO groups. The Hb content and LDH activity in the eluate were significantly lower in the NO groups than in the control group. These results indicate that addition of higher concentrations of NO was associated with a lower likelihood of coagulation on the dialyzer and in the dialysis circuit and a higher likelihood of smooth and successful 4-hour dialysis sessions. Addition of NO was associated with little risk of adverse effects such as met-Hb accumulation and reduction of blood pressure. Therefore, 800 ppm is considered as the most appropriate concentration of NO to be added to the dialysate for effectively inhibiting blood coagulation without causing any adverse effects. Conclusion Our experiment in a rat hemodialysis model showed that 800 ppm was the most appropriate concentration of NO to be added to the dialysate to suppress blood coagulation on the surface of the dialysis membrane without causing any adverse effects.

Development of Optical Sensing System for Noninvasive and Dynamic Monitoring of Thrombogenic Process

We developed a compact optical sensing system to monitor thrombogenic process noninvasively and dynamically by attaching a sensor on a blood circulating tubing. The system monitors the process for normal, erythrocyte aggregation, emboli, and thrombus formation stages with a continuously measured backscattered light. The system consists of an optical sensing unit, which has an 810-nm-wavelength chip light-emitting diode (LED) and a photodiode, and real-time monitoring software. The erythrocyte aggregation is verified by using the baseline transition of optical intensity, which is influenced by the apparent low number of red blood cells in erythrocyte-aggregated situation. Meanwhile, the emboli are evaluated by counting light-detected microembolic signals (LMES) induced by the flowing emboli. The performance of the system was evaluated using in vitro experiments with eight bovine blood samples. We performed optical sensing during thrombogenic process, which was intentionally generated by controlling the ratio of sodium citrate and calcium chloride solution. The activated whole blood clotting time (ACT) has gradually decreased in the process. The optical baseline transition has continuously increased at the beginning. After the increasing stopped, the LMES was observed. Finally, we found thrombus inside the mock-up circuit. As a result, we confirmed that our system is capable of monitoring the thrombogenic process noninvasively and dynamically.

Crush Syndrome after the Wenchuan Earthquake: New Experience with Regional Citrate Anticoagulation Continuous Veno-Venous Hemofiltration

Acute renal failure (ARF) related to crush syndrome is usually treated with hemodialysis. Continuous veno-venous hemofiltration (CVVH) has seldom been adopted in this situation due to the main drawback of continuous anticoagulation. The purpose of this study was to evaluate the effectiveness and safety of regional citrate anticoagulation (RCA)-CVVH in two crush syndrome patients following the Wenchaun earthquake. Two victims from the Wenchuan earthquake in Southwest China were admitted to our hospital on May 23, 2008, 11 days after their injury. The total entrapment time under the rubble was 5.5 and 22.5 hrs respectively. They remained oliguric on admission, in spite of vigorous treatment in the local hospital including aggressive fluid infusion, fasciotomy and intermittent hemodialysis. On admission, their serum myoglobin levels were 765 and 829 ng/mL, respectively. Further debridement and drainage were performed. RCA-CVVH was conducted; the citrate containing substitution fluid was infused in a pre-dilution manner at a rate of 4 l/h; calcium was infused through a separate access to the venous inlet of the double lumen catheter. The infusion rate was adjusted according to the serum ionized calcium and whole blood activated clotting time (WBACT). A low dose of low molecular weight heparin (LMWH) was infused at the rate of 150 approximately 300 U/h simultaneously for anticoagulation after anemia had been corrected and their wounds were stable. RCA-CVVH was substituted by conventional CVVH and LMWH anticoagulation when case 2 complicated with hypoxia. RCA-CVVH was well tolerated, hemodynamic status was stable, and no complications related with RCA-CVVH were noted. The body temperature and WBC decreased to normal range, while anemia and hypoalbuminia were corrected. The levels of serum myoglobin and creatine phosphokinase were also decreased to normal range. Their urine volume increased after 20 and 22 days of oliguria and the tubular function of the patients recovered well. Although the second case encountered acute cholecystitis and acute lung injury in the hospital, both the patients recuperated and neither of them underwent amputation. The present two crush patients have been successfully treated, but due to the limits of the small sample, it is difficult to generalize whether RCA-CVVH is safe enough for crush syndrome with a high risk of bleeding diathesis. Additional investigation with a larger number of patients is required. Fluid equilibrium, nutritional support, prevention of bleeding and infection are fundamental in this situation.

Evaluation of Optical Propagation in Blood for Noninvasive Detection of Prethrombus Blood Condition

This article evaluates the optical propagation to detect a "prethrombus" blood noninvasively. Thrombosis is still an inevitable issue in use of blood pumps, and it is required to predict thrombus formation as early as possible. We focused on the red blood cell (RBC) aggregation that is one of the features of thrombogenic process. First, by using a computer simulation, we calculated the optical propagations in blood for the RBC aggregation and nonaggregation blood. This simulation is based on the Monte-Carlo method and attempts to calculate the optical characteristics of the blood stochastically. In our simulation, the optical propagation with the RBC aggregation showed a different characteristic from that of the nonaggregation. Next, we examined the optical propagation in bovine blood with various activated whole blood clotting time (ACT). The blood mixed with sodium citrate was circulated by a blood pump. The ACT was adjusted between 1,000 and 50 seconds by controlling the ratio of calcium chloride solution to sodium citrate. We confirmed the RBC aggregation by using microscopic images and microthromboses in the pump directly. As a result, we evaluated that the change of the optical propagation has a correlation with thrombogenic process just as it was observed in our computer simulation. Our data indicate that the measurement of optical propagation can detect a prethrombous blood condition with RBC aggregation. Our study will help to establish optical technologies to detect prethrombous continuously and noninvasively.

Regional Citrate Anticoagulation during Hemodialysis

Background: Regional citrate anticoagulation during hemodialysis is promising, but its clinical implementation is routinely cumbersome because a continuous adjustment of calcium infusion at the dialyzer outlet is needed. Duocart biofiltration (DCB) is a new hemodialysis method using a calcium and magnesium-free dialysate containing only sodium chloride and bicarbonate combined with the infusion into the venous line of a solution containing the ionic complement (K, Ca, Mg) and glucose. Since the dialysate is calcium- and magnesium-free and infusion rate of the solution containing calcium is automatically determined by the dialysis delivery system according to the on-line measured value of ionic dialysance, DCB seems a technique especially suitable for citrate anticoagulation procedure. Methods: Thirty DCB sessions were performed in 10 patients with increased risk of bleeding. A commercially available mixture of trisodium citrate, citric acid and glucose was infused into the arterial line at a rate equal to 3% of dialyzer blood flow. The ionic complement (K: 48 mM, Ca: 42 mM, Mg: 14 mM, glucose: 110 mM) was infused at a rate equal to 1/24 ionic dialysance value automatically determined each 15 min by the dialysis monitor. DCB sessions were compared to 21 conventional bicarbonate hemodialysis (BHD) sessions with low-molecular-weight heparin anticoagulation. Results: Whole blood activated clotting time (WBACT) measured in the venous line (before infusion of ionic complement) was 200% of the WBACT value in the arterial line. Clotting and citrate-related adverse events were not observed. Postdialysis compression time of the arteriovenous access is significantly (p < 0.001) shorter after DCB sessions (3.9 ± 1.1 min) compared with BHD sessions (8.7 ± 4.6 min). Conclusion: Citrate anticoagulation during Duocart biofiltration is effective, safe and suitable for routine use because calcium infusion rate is automatically adjusted without the need of monitoring degree of anticoagulation and level of ionized calcium.

Monitoring of the heparin therapy during acute haemodialysis

Anticoagulation during renal replacement therapy is recommended to avoid thrombosis of the filter devices and to maintain the blood flow. However, in the case of multiorgan failure and sepsis, an imminent bleeding complication in patients with acute renal failure may cause the need for an extracorporeal circulation without anticoagulation. The most common drug used in renal replacement therapy is the unfractionated heparin (UFH). With low molecular weight heparin (LMWH) good experiences are reported, too. Based on the level of evidence from clinical studies plasma measurement of heparin is indispensable for patients with renal insufficiency. The activated whole blood clotting time (ACT), the activated partial thromboplastin time (aPTT), and the determination of the anti-factor Xa activity (anti Xa) with chromogenic substrates are available as routine as well as as point-of-care tests. To monitor plasma levels of LMWH the anti Xa assay serves exclusively as a suitable monitoring. The anti Xa assay using chromogenic substrates is the most specific and valid one for monitoring heparin therapy. In lack of large controlled studies for the anticoagulation therapy and its monitoring with the anti Xa test in acute renal failure, the current experiences are based on the results of chronic renal replacement therapy.

Überwachung der Heparintherapie bei Akutdialysen

ZusammenfassungDie Antikoagulation im Rahmen einer Nierenersatztherapie ist notwendig, um die Thrombosierung der Filter zu verhindern und den Blutfluss zu erhalten. Ausnahmen bilden Patienten mit akutem Nierenversagen und Begleiterkrankungen (z. B. Sepsis, Multiorganversagen), bei denen eine drohende Blutung das extrakorporale Verfahren auch ohne Antikoagulation erfordern kann.Am häufigsten wird unfraktioniertes Heparin als Antikoagulanz eingesetzt. Mit niedermolekularen Heparinen liegen ebenfalls positive Erfahrungen vor. Zur sicheren Therapieführung ist ein Monitoring der Antikoagulation notwendig. Die aktivierte Vollblut-Gerinnungszeit (ACT), die aktivierte partielle Thromboplastinzeit (aPTT) und die Anti-Faktor-Xa-Bestimmung mit chromogenen Substraten stehen als Routine- und Point-of-Care-Tests zur Verfügung. Zum Monitoring der niedermolekularen Heparine (NMH) kann nur die Anti-Faktor-Xa-Messung eingesetzt werden. Die spezifischste und valideste Methode für das Therapiemonitoring der Heparine ist der Anti-Faktor-Xa-Test mit Hilfe chromogener Substrate. Da wenig kontrollierte Studien zur Antikoagulanzientherapie und Monitoring mit dem Anti-Faktor-Xa-Test in der akuten Nierenersatztherapie vorliegen, beruhen die Empfehlungen auf den Erfahrungen mit der chronischen Nierenersatztherapie.

The diagnostic accuracy of bedside and laboratory coagulation: procedures used to monitor the anticoagulation status of patients treated with heparin.

We evaluated the diagnostic accuracy of three bedside coagulation procedures, the Hemochron activated whole-blood clotting time (ACT) (International Technidyne, Edison, NJ), the CoaguChek Plus (Boehringer Mannheim, Indianapolis, Ind) activated partial thromboplastin time (APTT) and the TAS (Cardiovascular Diagnostics, Raleigh, NC) APTT, before removal of arterial sheaths, in patients who received heparin therapy during percutaneous coronary angioplasty. As part of the postprocedure care, nurses performed bedside coagulation tests, removed the sheaths when appropriate coagulation criteria were met, and collected samples for laboratory APTT determinations and heparin assays performed with an automated chromogenic anti-Xa assay. Patients with heparin concentrations of 0.3 U/mL or more were classified as anticoagulated and those with concentrations less than 0.3 U/mL, as not anticoagulated. Analysis of the receiver operator characteristic (ROC) curve was used to rank the performance of the methods. Areas under the ROC curves +/- SE for the laboratory APTT, CoaguChek Plus APTT, Hemochron ACT, and TAS APTT were 0.978 +/- 0.016, 0.872 +/- 0.044, 0.797 +/- 0.039, and 0.795 +/- 0.048, respectively. At cutoff values for the tests that provide greatest safety for the patients (no false-negative results), the false-positive rates for the laboratory, CoaguChek Plus, Hemochron, and TAS methods were 15%, 27%, 62%, and 100%, respectively. The laboratory APTT demonstrated the highest diagnostic accuracy in this application; however, turnaround time for the test (50% of the results were reported in excess of 77 minutes) was inadequate for clinical decision making. To meet this requirement, we developed a point-of-care program using the whole blood APTT performed on the CoaguChek Plus analyzer.

Development of argatroban, a direct thrombin inhibitor, and its clinical application.

Argatroban, a direct thrombin inhibitor, is used clinically because of its safe and effective antithrombotic action. This drug of low molecular weight shows reversible inhibition of thrombin irrespective of whether thrombin is fibrin-bound or soluble. Optimal anticoagulant effects can easily be attained by monitoring with the activated partial thromboplastin time or whole-blood activated clotting time when a therapeutic range of argatroban equivalent to that of heparin is used. The antithrombotic action is simply detected with a chromogenic substrate assay. The clinical use of the drug in Japan was approved for the treatment of chronic peripheral arterial obstructive disease and acute ischemic stroke. For coronary artery disease in patients with deficiency of antithrombin activities attributable to either antithrombin III or heparin cofactor II deficiency, argatroban is effective as an anticoagulant. Acute coronary occlusion during and after percutaneous transluminal coronary angioplasty can be treated by argatroban as an alternative to heparin. The presence of platelets activated by a trace amount of thrombin is evidenced by modified methods of platelet aggregometry in acute ischemic stroke. Therefore, argatroban can render the platelets insensitive against the platelet hyperaggregation enhanced by thrombin.

Critical, Acutely Poisoned Patients Treated With Continuous Arteriovenous Hemoperfusion in the Emergency Department

Study objective: To investigate the efficiency of a new nonpump hemoperfusion technique, continuous arteriovenous hemoperfusion, in the treatment of critical, acutely poisoned patients. Setting: Emergency department of a general hospital. Participants: Acutely poisoned patients who failed to respond to intensive supportive treatment and needed hemoperfusion therapy. Interventions: All patients received continuous arteriovenous hemoperfusion therapy for 4 to 8 hours. Toxicant clearances were determined by obtaining serial theophylline and phenobarbital levels every 2 hours before, during, and after continuous arteriovenous hemoperfusion. Platelet counts, whole-blood activated clotting time, and vital signs were monitored. Results: The clinical condition of these patients improved rapidly after continuous arteriovenous hemoperfusion was started. The treatments were performed easily, and no significant complications occurred. The clearances of theophylline and phenobarbital were 192.79±1.55 mL/min and 290.25±25.33 mL/min, respectively, similar to those of conventional hemoperfusion. Conclusion: Continuous arteriovenous hemoperfusion is a simple, safe, effective, and less costly alternative to conventional hemoperfusion, especially in the EDs of hospitals without hemoperfusion facilities immediately available. [Lin J-L, Jeng L-B: Critical, acutely poisoned patients treated with continuous arteriovenous hemoperfusion in the emergency department. Ann Emerg Med January 1995;25:75-80.]

Citrate versus heparin anticoagulation in chronic haernodialysis patients

Anticoagulation with citrate at a rate of 0.68 mM/min in combination with a calcium and magnesium-free dialysate and i.v. supplementation of calcium and magnesium at rates of 0.18 mM/min and 0.08 mM/min respectively, was compared with low-dose heparin. The heparin dose was a loading dose of 2500 IU and a sustaining infusion of 750-1250 IU/h; or a loading dose of 1250 IU and a sustaining infusion of 500-750 IU/h until 1 h before the end of the dialysis if the patient was taking concomitantly coumarin anticoagulation for a Goretex shunt. Six chronic haemodialysis patients changed from heparin to citrate anticoagulation because they reported bleeding between dialyses. Heparin, after 2 h dialysis, induced a significant 10% prolongation of each patient's whole-blood activated clotting time (WBACT) as compared to the predialysis value; while the WBACT at the dialyser outlet was less than 3% prolonged as compared to the patient's WBACT. However, after 2 h citrate the patient's WBACT was not prolonged but the WBACT at the dialyser outlet was 20-100% longer, indicating a better anticoagulation of the extracorporeal system without systemic effects. With heparin the shunt pressure time (SPT), i.e. the time needed to stop bleeding from the puncture sites of the Goretex shunts, was 12 of 28 times 20 min or more. Citrate reduced these episodes by 75%. Thus citrate should be considered for chronic haemodialysis patients who are at risk of bleeding because of the concomitant use of anticoagulants.(ABSTRACT TRUNCATED AT 250 WORDS)

Low-Molecular-Weight Heparin Fraxiparin® in Chronic Hemodialysis

A two-step dose-ranging study was undertaken with CY216 (Fraxiparin) in 8 patients on 7 sessions each. The different doses were administered each time as a single bolus injection at the start of hemodialysis without heparinized priming nor further administration during the 4-hour session. In the first step, the clinical efficacy of 4 different doses of Fraxiparin was compared with that of standard heparin on the percentage of sessions free of clot formation in the extracorporeal circulation (ECC). Safety was evaluated by the compression time for hemostasis at the puncture sites. The second step was a randomized comparison of 3 Fraxiparin dosages. In addition to the clinical assessment of efficacy, the following biological parameters were measured: fibrinopeptide A (FPA), anti-Xa (AXa) activity calibrated against Fraxiparin, thrombin time (TT), activated partial thromboplastin time, blood counts, hemoglobin, hematocrit, plasma creatinine and urea, and residual blood volume in the dialyzer. A 'standard' dosage of 10,000 AXa Institut Choay units of Fraxiparin was shown to prevent clot formation in the ECC. It resulted in a marked increase in TT, without any lengthening of the puncture site compression time. After 4 h, AXa and FPA levels in the venous line were related to the doses used (p less than 0.05). After 48 h AXa activity was very low. Dialysance and tolerance were excellent. Thus, a single dose of Fraxiparin unrelated to body weight and not determined by the measurement of the whole-blood activated clotting time appeared to be a safe and effective means for preventing fibrin formation in 4-hour dialysis sessions.

A simplified method for monitoring heparin therapy at the bedside: the activated whole blood clotting time.

Twelve patients receiving heparin during hemodialysis had coagulation parameters monitored using the whole blood clotting time (WBCT), activated partial thromboplastin time (APTT), plasma heparin levels and activated whole blood clotting time (AWBCT). The AWBCT, performed with a battery-powered portable incubator/timer, correlated with both the corresponding WBCT and the plasma heparin levels. However, the correlation between the AWBCT and the APTT was quite poor. This assay is simply performed, inexpensive, and reproducible. It is recommended as an excellent method for monitoring heparin therapy.

Evaluation of the activated whole blood clotting time (ACT) in vitro.

The activated whole blood clotting time (ACT) was analyzed in vitro using blood samples from normal individuals and from patients with heart disease, scheduled for open heart surgery. The ACT was found to be normally distributed in a group of normal individuals with a mean of 135 sec. In patients with heart diseases, the average ACT was slightly shorter than in normal individuals. A linear relationship between ACT and heparin concentrations was established. Haemodilution and depletion of platelets did not significantly influence the ACT. When a clean venipuncture with disposable needles is used, ACT is a reliable, uncomplicated bedside technique by which heparinisation can be monitored.

Anticoagulant Kinetics Following Bolus Injection of Heparin

SummaryBolus injections of beef-lung heparin at doses of 50, 100 and 200 u/kg body weight were administered to mongrel dogs. Neutralization of the anticoagulant effect was evaluated using sequential samples withdrawn from the animals (in vivo samples) and aliquots from a 100 ml sample withdrawn from the dog at 30 minutes post-injection (in vitro samples). Tests of the activated partial thromboplastin time (APTT) and prothrombin time (PT) did not indicate the degree of anticoagulation. Tests of the whole blood clotting time (WBCT), celite- activated whole blood clotting time (ACT), and celite-activated thromboelastography (ATEG) indicated pronounced hypocoagulability immediately after the injection, followed by a fairly rapid decay in anticoagulability, and a slight Ziype/coagulability at three to four hours post injection. The results from the in vitro ATEG samples were essentially identical to those on the in vivo samples, whereas the in vitro WBCT and ACT generally indicated higher degrees of anticoagulation. Calculated half-lives of the anticoagulant effect are significantly shorter than previously reported, being 18 to 36 minutes, and slightly dose dependent. The decay of the effects, however, does not appear to follow a single exponential curve, dropping very rapidly immediately post-injection and at a somewhat slower rate 60 or more minutes post-injection.

Adequate Anticoagulation During Cardiopulmonary Bypass Determined by Activated Clotting Time and the Appearance of Fibrin Monomer

The adequacy of anticoagulation during 2 hours of cardiopulmonary bypass at 30° in 9 rhesus monkeys was determined by measuring the whole-blood activated clotting time (ACT) and by noting the appearance of thrombin-altered fibrin (fibrin monomer) and the relative consumption of clotting factors. Factors V and VIII, the heparin cofactor, antithrombin III, prothrombin time, partial thromboplastin time, ACT, platelets, hematocrit, fibrinogen, and fibrin monomer were determined prior to heparinization and after protamine. In 6 of 9 experiments, fibrin monomer became positive in the plasma during cardiopulmonary bypass (CPB), indicating that active coagulation was occurring. In 5 of the 6 animals, initial ACT was less than 400 seconds, and fibrin monomer appeared within the first 30 minutes of bypass. In 1 animal with an initial ACT of 439 seconds, fibrin monomer appeared after 60 minutes of bypass, at which time the ACT was less than 400 seconds. An abnormal level of fibrin monomer was not detected in 5 pediatric patients with an ACT greater than 450 seconds during CPB. Our experimental study and clinical data suggest that the lower limit, as measured by the ACT, for anticoagulant effect to provide coagulation-free CPB is at least 400 seconds.